Commercialization of a Benchtop Radiosynthesizer for the Production of PET Probes

用于生产 PET 探针的台式放射合成仪的商业化

• 批准号: 8250984
• 负责人: Melissa Moore
• 金额: $ 14.52万
• 依托单位: SOFIE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-09 至 2012-10-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250984
• 关键词: Affect; Automation; Basic Science; Biochemical; Biological; Biological Markers; Biological Process; Biology; Brain; Brain Diseases; Brain imaging; Capital; Cell Proliferation; Cells; Clinical; Clinical Research; Clinical Trials; Companions; Computers; Critical Pathways; Dependency; Detection; Development; Devices; Diagnostic; Disease; Dose; Early Diagnosis; Electronics; Ensure; Environment; Equipment; Evaluation; Event; Freedom; Functional disorder; Goals; Heating; High Pressure Liquid Chromatography; Human; Human Resources; Image; Incentives; Investments; Laboratories; Lead; Levodopa; Libraries; Liquid substance; Literature; Marketing; Measures; Medicine; Microfluidics; Miniaturization; Modeling; Monitor; Mus; Organic solvent product; Patient Care; Patients; Pharmaceutical Preparations; Phase; Positron-Emission Tomography; Price; Problem Solving; Process; Production; Public Health; Radiation; Radio; Radiochemistry; Radiolabeled; Reaction; Reagent; Reporting; Research; Research Infrastructure; Safety; Scientist; Site; Solutions; Structure; System; Technology; Temperature; Therapeutic; Time; Tracer; Training; Translating; Treatment Efficacy; Variant; Work; analytical tool; base; biological systems; chemical synthesis; clinically relevant; commercialization; cost; design; empowered; evaporation; flexibility; glucose analog; imaging modality; improved; interest; meetings; microorganism; molecular imaging; novel; operation; point of care; presynaptic; prototype; pyridine; radiotracer; tool; usability; user-friendly

DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) is a molecular imaging modality that utilizes radiolabeled molecules ("probes") to target and measure biological processes. Basic scientists can use the same probes to examine microorganisms, cells, and mice as they do in patients to visualize and characterize the biology of disease, monitor its progression, and evaluate therapeutic efficacy. Although over 1,600 PET probes have been developed to help answer a variety of biological questions, including many specific to understanding the structure and function of the human brain, only the glucose analog [18F]FDG is routinely used for molecular imaging diagnostics in patient care today. This limitation exists because of the centralized approach to PET probe production necessitated by the high cost of infrastructure, specialized equipment, and skilled personnel required for synthesis. Overcoming these hindrances to PET probe development, optimization, and routine production is necessary to facilitate the entry of numerous other promising PET probes into clinical research and trials, and to select those with value as companion biomarkers. A decentralized approach to PET probe development is required to give scientists the freedom to determine what probes they want to use to best solve the problems of their interest. This goal can be achieved by building a benchtop, PC-controlled, microfluidic chip-based commercial device for the on-demand production of PET probes. Phase I of this project will answer basic commercial feasibility questions about the underlying Electro- Wetting-On-Dielectric (EWOD) microfluidic chip technology. In Aim 1, we will develop a reagent loading system for a radiochemistry-based EWOD device that will enable full automation of on-chip syntheses for increased usability and safety. In Aim 2, we will demonstrate that the EWOD platform is capable of diverse syntheses by preparing additional PET compounds beyond the [18F]FDG proof-of-concept studies to date. The focus will be on compounds specifically relevant to brain imaging. Phase II will produce a commercial prototype of the device, complete with a PC-based control system that contains an inexpensive, disposable, probe-specific cartridge of the microfluidic chip and associated reagents. As an eventual product, a library of chips will be developed based on customer needs for different probes. Shifting to a point-of-research/point-of-care model is a transformational solution that removes the limitations imposed by the centralized model on probe production, cost, and diversity. By empowering scientists and clinicians to control the development and use of PET probes, they are able to focus on processes that they believe are most important. PUBLIC HEALTH RELEVANCE: Novel molecular imaging modalities to measure biochemical and cellular events in patients are needed in personalized medicine to transform the care of patients with brain disorders. The goal of this proposal is to develop an affordable, compact, chip-based device to produce PET probes, thereby enabling scientists to image diverse biological systems by eliminating barriers that currently limit probe availability and diversity. The scientific yield from this may lead to improved therapies for the pathophysiology of brain disorders, significantly affecting public health.

描述(申请人提供)：正电子发射断层扫描(PET)是一种利用放射性标记分子(“探针”)来瞄准和测量生物过程的分子成像方式。基础科学家可以使用与在患者身上相同的探针来检查微生物、细胞和小鼠，以可视化和表征疾病的生物学，监测其进展，并评估治疗效果。虽然已经开发了1600多个PET探针来帮助回答各种生物学问题，包括许多特定于了解人脑结构和功能的问题，但目前只有葡萄糖类似物[18F]FDG被常规用于患者护理中的分子成像诊断。存在这一限制的原因是，由于合成所需的基础设施、专门设备和熟练人员的高昂成本，需要采用集中化的方法来生产PET探头。克服这些障碍对PET探针的开发、优化和常规生产是必要的，以促进许多其他有前途的PET探针进入临床研究和试验，并选择那些有价值的作为伴随生物标记物。需要一种分散的方法来开发PET探针，以便让科学家自由决定他们想要使用什么探针来最好地解决他们感兴趣的问题。这一目标可以通过构建台式、PC控制的、基于微流控芯片的商业设备来实现，以按需生产PET探头。该项目的第一阶段将回答有关基础电介质润湿(EWOD)微流控芯片技术的基本商业可行性问题。在目标1中，我们将开发一种用于基于放射化学的EWOD设备的试剂加载系统，该系统将实现芯片上合成的完全自动化，以提高可用性和安全性。在目标2中，我们将证明EWOD平台能够通过在迄今的[18F]FDG概念验证研究之外制备更多的PET化合物来进行多样化的合成。重点将放在与大脑成像特别相关的化合物上。第二阶段将生产该设备的商业原型，并配有一个基于PC的控制系统，该系统包含一个廉价的、一次性的、探头专用的微流控芯片盒和相关试剂。作为最终产品，将根据客户对不同探头的需求开发芯片库。转向研究点/护理点模式是一种变革性的解决方案，它消除了集中式模式对探头生产、成本和多样性造成的限制。通过授权科学家和临床医生控制PET探头的开发和使用，他们能够专注于他们认为最重要的过程。 公共卫生相关性：个性化医学需要新的分子成像方法来测量患者的生化和细胞事件，以改变对脑部疾病患者的护理。这项提议的目标是开发一种负担得起的、紧凑的、基于芯片的设备来生产PET探针，从而使科学家能够通过消除目前限制探针可用性和多样性的障碍来成像不同的生物系统。由此产生的科学成果可能会改进脑部疾病的病理生理学治疗，从而显著影响公众健康。